Maternal high-fat diet exposure impairs LKB1-TGFβ1 inflammatory pathway and increases hypothalamic 5HT receptors gene

Wenicios Ferreira Chaves1, Suleyma de Oliveira Costa2, Nilton J Santos2

  • 1Graduate Program in Science of Nutrition, Sports and Metabolism, University of Campinas, UNICAMP, Limeira, SP, Brazil.

Brain Research
|May 17, 2025
PubMed

Insights

Maternal high-fat diet (HFD) exposure disrupts offspring brain development, leading to altered energy homeostasis. This study reveals molecular changes in the hypothalamic serotonergic system, impacting growth and metabolism.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Metabolic Research

Background:

  • The serotonergic system is crucial for regulating mood, feeding, and neurodevelopment.
  • Maternal high-fat diet (HFD) intake elevates proinflammatory cytokines, potentially impairing offspring brain development.
  • Understanding HFD's impact on the offspring's serotonergic system is vital for metabolic health.

Purpose of the Study:

  • To investigate the effects of maternal HFD exposure on offspring feeding behavior, somatic growth, and the hypothalamic serotonergic system.
  • To identify molecular alterations in the offspring's brain in response to maternal HFD.

Main Methods:

  • Wistar rats were used, with dams fed either a control or HFD.
  • Offspring were assessed for body weight, fat mass, food intake, and feeding behavior.
  • Hypothalamic gene expression and protein phosphorylation related to the serotonergic system and energy metabolism were analyzed.

Main Results:

  • Offspring from HFD-fed dams exhibited increased body weight, fat mass, and somatic growth.
  • Elevated hypothalamic gene expression of Htr1a, Htr2a, and Tgfb1 was observed.
  • Reduced phosphorylation of key signaling proteins (FoxO1, CREB, LKB1) was noted, without changes in leptin or insulin signaling.

Conclusions:

  • Maternal HFD exposure induces significant alterations in offspring's somatic growth and hypothalamic serotonergic signaling.
  • These changes suggest an early disruption in energy homeostasis, mediated by the serotonergic system.
  • Further research is needed to understand the long-term metabolic consequences.